Changes in CO2-Derived Variables, Induced by Passive Leg Raising Test, Detect Preload Responsiveness in Mechanically Ventilated Patients: A Pilot Study

<b>Background/Objectives.</b> Changes in CO₂-derived variables during a fluid challenge have been proposed as markers of fluid responsiveness. We investigated whether, instead of fluid administration, passive leg raising (PLR)-induced changes in the CO₂-derived variables, namely central venous-arterial carbon dioxide partial pressure (P(cv-a)CO₂) and the ratio between P(cv-a)CO₂ and the arterial-central venous oxygen content (P(cv-a)CO₂/C(a-cv)O₂), could detect preload responsiveness in critically ill patients. <b>Methods.</b> We studied 30 mechanically ventilated patients in whom a PLR test was performed due to acute circulatory failure. Routine hemodynamic variables, velocity-time integral (VTI), in the left ventricular outflow tract, and CO₂-derived variables, were measured before, during, and after a PLR test. A PLR-induced increase in VTI of ≥10% defined preload responsiveness. The differences (Δ) of P(cv-a)CO₂ and P(cv-a)CO₂/C(a-cv)O₂ between PLR and pre-PLR were calculated. The predictive values of PLR-induced changes in the CO₂-derived variables was determined by receiver operating characteristic area under curves (ROC-AUCs). <b>Results.</b> Fifteen patients (50%) were classified as preload responsive. ΔP(cv-a)CO₂ and ΔP(cv-a)CO₂/C(a-cv)O₂ were correlated with VTI changes and differed significantly between responders and non-responders -1.3 (-2--0.6) vs. 0.6 (-0.1-1.1) mmHg, <i>p</i> < 0.001, and -0.38 (-0.97--0.34) vs. 0.1 (-0.15-0.57) mmHg/mL O₂, <i>p</i> < 0.001, respectively. The PLR-induced decrease in P(cv-a)CO₂ was significantly associated with preload responsiveness (OR 0.48, CI 0.20-0.89, <i>p</i> = 0.016, bootstrap CI 0-0.85). The AUC curves for both ΔP(cv-a)CO₂ and ΔP(cv-a)CO₂/C(a-cv)O₂ ratio to predict preload responsiveness were 0.89 (CI 0.74-1), <i>p</i> < 0.001, and 0.85 (CI 0.70-1), <i>p</i> < 0.001, respectively. <b>Conclusions.</b> In mechanically ventilated ICU patients with circulatory shock, PLR-induced changes in P(cv-a)CO₂ and P(cv-a)CO₂/C(a-cv)O₂ ratio were correlated with VTI changes. The change in P(cv-a)CO₂ was the only variable detecting preload responsiveness assessed by PLR; therefore, it could serve as an indirect marker, useful to guide fluid resuscitation when cardiac output measurement is not feasible.